Project Summary Cardiovascular diseases claim more than 17 million lives worldwide every year. In the United States alone, 92.1 million people are affected by cardiovascular disease, and 32% of all major deaths are attributed to it. A portion of the cardiovascular disease population has abnormalities that necessitate implantation of a pacemaker to maintain normal heart rhythm. A pacemaker is a device that sends regular electrical impulses to the heart via long wires called leads connected to a generator placed underneath the skin. In the United States alone, pacemakers are implanted in more than 370,000 patients annually. Complications related to pacemaker implantation occur in 10% of these patients. These complications are largely device-related and include lead failure, lead dislodgement, infection, tricuspid regurgitation, and venous occlusion. Recent developments in pacemaker technology have led to leadless pacemakers, which have shrunk the pacemaker into a bullet-sized device that can be implanted inside the heart. However, these devices in their current form factor are too bulky to provide therapy to pediatric patients. To address this problem, we developed a miniature (11 mm 11 mm), leadless, wirelessly powered pacing device that can pace multiple locations across the heart synchronously. Our successful experiments in pacing multiple chambers of the heart in vivo has led to the hypothesis that this approach of multisite pacing will our technology will enable the development of miniature devices that will provide leadless, wirelessly powered means of pacing at unprecedented numbers of sites and in previously inaccessible regions, thereby enhancing myocardial synchronization and conduction. In this proposal, we aim to develop a system comprising of a distributed network of wirelessly powered pacing and sensing nodes (SA 1) that can be controlled by a data-driven algorithm (SA 2) to provide optimal cardiac resynchronization therapy. This system will be iteratively developed and validated in a subacute in vivo porcine model of heart failure (SA 3). Drs. Babakhani, Cavallaro, and Lin will each contribute to the hardware development. Dr. Aazhang will supervise the development of the data-driven algorithm, and Dr. Razavi will oversee device development and all animal studies. Research outcomes from this project will improve our understanding of wireless power transfer, lead to the creation of novel intracorporeal inter-device communication protocols, and offer an innovative approach to pacing therapies. The device in its refined state will be small enough for transvenous delivery, capable of synchronous pacing and sensing from multiple locations, and deliver appropriate personalized therapy by using algorithms to detect patient-specific rhythm abnormalities. Such a device will have far-reaching clinical impact by allowing pacing at multiple locations, including those that were previously inaccessible. Furthermore, the device will normalize conduction across a damaged heart to better manage arrhythmia and can provide imperceptible low-energy defibrillation for painless cardioversion.